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1.
Int Wound J ; 17(1): 100-106, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31701658

RESUMO

The objective of this study is to investigate the mechanism whereby innate immune molecule surfactant protein D (SP-D) attenuates sepsis-induced acute kidney injury (AKI) through modulating apoptosis and nuclear factor kappa-B (NFκB)-mediated inflammation. In the present study, a mouse sepsis model was established by cecal ligation and puncture in SP-D knockout (KO) mice and wild-type (WT) mice. A sham-operated group was included as the control. The experimental materials were extracted 6 and 24 hours postoperatively. The plasma levels of tumour necrosis factor alpha (TNF-α) and MCP-1 were determined by enzyme-linked immunosorbent assay (ELISA). Apoptosis was measured by double staining with Annexin V/propidium iodide and flow cytometry. The levels of NFκB in renal tissues were measured by ELISA and Western blotting assay. Apoptosis was detected by TUNEL assays. There were no significant differences in plasma TNF-α levels between the WT sham group and the KO sham group at 6 and 24 hours postoperatively (P < .05), but the levels of TNF-α in the WT sepsis and KO sepsis groups were significantly higher than those in controls (P < .05). The levels of TNF-α in the KO sepsis group were significantly higher than those of the WT sepsis group (P < .05). TNF-α levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The levels of MCP-1 in the WT sepsis group and the KO sepsis group at 6 and 24 hours postoperatively were significantly higher than those in the control group (P < .05), and MCP-1 levels in the KO sepsis group were significantly higher than those in the WT sepsis group (P < .05). MCP-1 levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The expression of SP-D in WT kidneys was significantly lower at 6 and 24 hours postoperatively (P < .05). The number of TUNEL-positive cells in the kidneys from septic SP-D KO mice was significantly higher (P < .05). The levels of NFκB in septic mice were significantly increased at 6 and 24 hours after induction of sepsis compared with the sham-operated group compared with those of septic SP-D KO mice and WT mice (P < .05). Innate immune molecule SP-D significantly decreased plasma levels of inflammatory cytokines in mice and attenuated sepsis-induced AKI by inhibiting NFκB activity and apoptosis.

2.
Arch Med Res ; 50(6): 368-376, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31678895

RESUMO

BACKGROUND: This study aims to evaluate whether the Vitamin D receptor (VDR) gene polymorphisms were associated with systemic sclerosis (SSc) in a Chinese Han population. METHODS: Using a hospital-based case-control study including 100 SSc patients and 100 healthy controls. Single nucleotide polymorphisms (SNPs) in the VDR region were genotyped by the improved multiplex ligase detection reaction (i MLDR) method. Haplotypes were also constructed after linkage disequilibrium (LD) analysis. RESULTS: Eight SNPs (rs731236 (TaqI), rs2228570 (FokI), rs7975232 (ApaI), rs1544410 (BsmI), rs11574010 (Cdx2), rs739837 (BglI), rs757343 (Tru9I) and rs11168267) were included. There were significant differences between SSc patients and healthy individuals in ApaI and BglI genotype (both adjusted p = 0.008). Through the genotyping, significantly association of SSc were found for: dominant model of ApaI and BglI (both OR (95% CI) = 1.80 (1.03,3.16), p = 0.040). Furthermore, the elevation of erythrocyte sedimentation rate (ESR) had a higher percentage of BglI GT genotype frequency (p = 0.034) and dominant model of ApaI (p = 0.016) in SSc. There was high linkage disequilibrium was detected in BglI and ApaI polymorphisms (r2 = 1.0, D' = 1.0), Tru9I and rs11168267 (r2 = 0.926, D' = 0.969), respectively. No significant difference were found in these four haplotypes (all p >0.05). The correlation between VD levels and VDR gene polymorphisms was not statistically significant. CONCLUSIONS: Our preliminary study indicates the ApaI and BglI genotype may possibly have a role in the pathogenesis of SSc patients. Dominant model of ApaI and BglI GT genotype frequency may be associated with the increased risk of ESR.

3.
Clin Rheumatol ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31691041

RESUMO

OBJECTIVES: To explore the prevalence and risk factors of osteoporosis (OP) and vertebral osteoporotic fracture (VOPF) in patients with rheumatoid arthritis (RA). METHODS: Anteroposterior and lateral X-ray examination of the vertebral column (T4-L4) was used for the semi-quantitative assessment of VOPF. Bone mineral density was measured by dual-energy X-ray absorptiometry. RESULTS: Of 865 RA patients, the prevalence of OP and VOPF was 33.6% and 20.2%, respectively. Patients with OP or VOPF were older, and had longer term use and a larger daily amount and cumulative dose of glucocorticoids (GCs), longer disease duration, and higher Health Assessment Questionnaire (HAQ) scores and Sharp scores than patients without OP or VOPF (P < 0.05). OP was also correlated with higher disease activity. The patients treated with GCs had higher incidences of OP and VOPF than the patients without GCs (P < 0.05). The cutoff values in the area under curve (AUC) of the daily dose or treatment course of GCs-VOPF were 9 mg and 37.5 days. Older age, female sex, and a higher Sharp score were risk factors for OP in RA patients, while higher BMI was a protective factor. Older age and a high GC daily dose were risk factors for VOPF in RA patients. CONCLUSIONS: RA patients have a high prevalence of OP and VOPF. Older age, female sex, lower BMI, and higher activity and severity of RA are closely related with OP. Older age and a higher GC daily dose are risk factors for VOPF in RA patients. Key Points • Older age, female sex, lower BMI, and a higher Sharp score were risk factors for OP in RA patients. • Older age and a high GC daily dose were risk factors for VOPF in RA patients. • OP and VOPF in RA patients were correlated with longer disease duration and higher severity of RA.

4.
Int J Rheum Dis ; 22(10): 1832-1840, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31464381

RESUMO

AIM: To examine the associations between female menstrual or reproductive factors and the development of systemic sclerosis (SSc) in China. METHODS: In this hospital-based case-control study, for each subject, data on reproductive and menstrual factors such as number of births, abortions, and age at menarche were obtained by structured questionnaire. Risk estimates, measured by the odds ratio (OR) and 95% confidence interval (CI), were obtained by unconditional logistics regression. Furthermore, meta-analysis was performed and pooled OR with 95% CI for the number of pregnancies and abortions were calculated. RESULTS: There were 166 SSc and 392 female controls seen during the study period. The results showed women with late menarche age (≥17 years) were less likely than those with earlier age at menarche to develop SSc (OR 0.347, 95% CI 0.174-0.693) and compared with women without abortion, women with abortion (1 time) were at reduced risk of developing SSc (P = .036). After adjusting for potential confounders such as occupation and body mass index (BMI), late age at menarche (≥17 years) was associated with a decreased risk of SSc (OR 0.187, 95% CI 0.068-0.513), but abortions were not significantly related to SSc. The meta-analysis revealed there was no association between SSc and abortions or number of pregnancies. No significant publication bias was observed (P > .05). CONCLUSION: Late age at menarche was associated with a reduced risk of SSc but abortion may not be an independent risk factor for SSc. Further investigations are required to verify our findings.

5.
Cancer Manag Res ; 11: 5871-5882, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303793

RESUMO

Background: ZNF488 acts as an oncogene which promotes cell invasion and endows tumor cells stem cell capacity in nasopharyngeal carcinoma (NPC), but its correlation with clinicopathologic characteristics and patients' survival in NPC remain undefined. Methods: In this study, 158 cases of confirmed NPC were subjected to immunohistochemistry staining for evaluating endogenous expression. Kaplan-Meier method and log-rank test were used to estimate the survival rates. The relationship between ZNF488 and clinicopathological characteristics was statistically calculated by chi-squared test, univariate and multivariate analysis. In addition, adhesion assay, MTT and colony formation assays were performed for measuring adhesion and proliferation capacity. Cell cycle analysis via flow cytometry was conducted to explore cell cycle distribution. Western blot was used to detect pathway protein levels, and the pFAK (Y397) kit was used for focal adhesion kinase (FAK) activation. Results: We demonstrated that high expression of ZNF488 was significantly correlated with locoregional failure (P=0.018) and distant metastasis (P=0.001). Patients with high ZNF488 expression had poorer overall survival (P<0.001), loco-regional recurrence-free survival (P<0.001), distance metastasis-free survival (P<0.001) and progression-free survival (P<0.001) than those with low ZNF488 group. Multivariate analysis showed that ZNF488 expression was an independent prognostic indicator for predicting NPC patients' survival (HR, 3.314; 95% CI, 1.489-7.386; P=0.003). Additionally, ZNF488-induced collagen IV/FAK/AKT to enhance adhesion ability meanwhile led to the upregulation of Cyclin D1 to facilitate cell proliferation through promoting cell cycle progression and inhibition of apoptosis through caspase-independent way. Conclusion: These results reveal that ZNF488, as an independent prognostic indicator, promotes cell adhesion and proliferation through collagen IV/FAK/AKT/Cyclin D1 pathway in NPC.

6.
Beilstein J Nanotechnol ; 10: 1237-1242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293861

RESUMO

Tb2.96- x Ce0.04GdxAl5O12 phosphors were synthesized through solid-state reactions. The influence of Gd3+ on the luminescence was investigated. Under the excitation at 460 nm, Tb2.96Ce0.04Al5O12 shows the characteristic emission band of Ce3+ with a peak wavelength at about 554 nm. After co-doping Gd3+ into Tb2.96Ce0.04Al5O12, the peak wavelength of the Ce3+ emission band shifts to longer wavelengths, which is induced by the increasing crystal field splitting. However, the Ce3+ emission intensity also decreases because the substitution of Tb3+ with Gd3+ causes lattice deformation and generates numerous structural and chemical defects. By comparing the light parameters of white light-emitting diodes (WLEDs) containing Y2.96Ce0.04Al5O12, Tb2.96Ce0.04Al5O12 and Tb2.81Ce0.04Gd0.15Al5O12 phosphors, we can find that the WLED containing the Tb2.81Ce0.04Gd0.15Al5O12 phosphor generates warmer light than the WLEDs containing Y2.96Ce0.04Al5O12 and Tb2.96Ce0.04Al5O12 phosphors. Moreover, the WLEDs fabricated by integrating a blue LED chip and Ce3+/Gd3+-co-doped Tb3Al5O12 phosphors show outstanding colour stability when driven under different currents.

7.
Nat Prod Res ; : 1-7, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31230492

RESUMO

A new demethyl abietane diterpenoid, Triptotin K (3) together with three known compounds, friedelin (1), canophyllal (2), and triptonoterpene (4) were isolated from the roots of Tripterygium wilfordii Hook. f. by silica gel column and preparative high performance liquid chromatography. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Triptotin K showed cytotoxic activities against KB, KBv200, HepG2, and MCF-7/ADM cells lines with IC50 values of 29.88, 36.50, 39.55, and 41.38 µM, respectively.

8.
Protein Sci ; 28(5): 971-975, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30834616

RESUMO

The bacterial type VI secretion system (T6SS) utilizes many toxic effectors to gain advantage over interbacterial competition and eukaryotic host infection. Meanwhile, the cognate immunity proteins of these effectors are employed to protect themselves from the virulence. TseT and TsiT form an effector-immunity (E-I) protein pair secreted by T6SS of Pseudomonas aeruginosa. TseT is toxic for other bacteria, whereas TsiT can suppress the virulence of TseT. Here, we report the crystal structure of TsiT at 1.6 Å resolution. TsiT is a typical α + ß class protein and belongs to a novel Imm52 protein family of the polymorphic toxin system. Apart from TsiT, only one structure of the Imm52 family proteins is present in the Protein Data Bank (PDB), but that structure is not characterized and shares low sequence identity with TsiT. We characterized the basic features of TsiT structure and identified conserved residues of the Imm52 family proteins according to homology comparison. Our work provided structural information of a new protein family and should aid future functional studies.

9.
J Clin Rheumatol ; 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30768443

RESUMO

OBJECTIVES: The aim of this study is to investigate whether heat shock protein 70 (Hsp70) gene polymorphisms are implicated in systemic lupus erythematous (SLE) susceptibility, the efficacy of glucocorticoids (GCs) treatment, and improvement of health-related quality of life. METHODS: A total of 499 SLE patients and 499 controls were included in a case-control study, and 468 SLE patients treated with GCs for 12 weeks were involved in a follow-up study. Patients who completed the 12-week follow-up were divided into GCs-sensitive and GCs-insensitive group by using the SLE disease activity index. The SF-36 was used to evaluate the health-related quality of life of SLE patients, and genotyping was performed by improved multiplex ligation detection reaction. RESULTS: rs2075800 was associated with SLE susceptibility (adjusted odds ratio [ORadj], 1.437; 95% confidence interval [CI], 1.113-1.855; Padj = 0.005; PBH = 0.020 by dominant model; ORadj, 1.602; 95% CI, 1.072-2.395; Padj = 0.022; PBH = 0.029 by TT vs CC model; ORadj = 1.396; 95% CI = 1.067-1.826; Padj = 0.015; PBH = 0.029 by TC vs CC model). In the follow-up study, rs2075799 was associated with the improvement in mental health (p = 0.004, PBH = 0.044), but we failed to find any association between the efficacy of GCs and Hsp70 gene polymorphisms. CONCLUSIONS: Hsp70 gene polymorphisms may be associated with susceptibility to SLE and improvement of mental health in Chinese Han population.

10.
Gene ; 692: 54-59, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30641221

RESUMO

OBJECTIVE: Obesity is one of the major health problems strongly influenced by lifestyle, genetic and environmental factors. Previous studies have reported many single-nucleotide polymorphisms (SNPs) are associated with obesity in different races. This study aimed to explore the genetic associations between LEPR, MC4R polymorphisms and overweight/obesity in Chinese Han adolescents. METHODS: 400 adolescents including 222 health controls and 178 overweight/obese adolescents were genotyped and their body compositions were also analyzed in this study. RESULTS: We found that allelic and genotypic frequencies of LEPR SNP rs8179183 were significantly different between controls and cases (allelic frequency p < 0.001; genotypic frequency p = 0.004). These difference was still significant (allelic frequency p < 0.011; genotypic frequency p = 0.024) after Bonferroni correction. Moreover, we found that rs8179183 was associated with serum triglyceride level after adjusting for age and body mass index (BMI) (p = 0.037). CONCLUSION: In summary, our results found a significant association between LEPR SNP rs8179183 and overweight/obesity in Chinese Han adolescent. This study may provide a reference for future studies of obesity.


Assuntos
Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Receptor Tipo 4 de Melanocortina/genética , Receptores para Leptina/genética , Adolescente , Apolipoproteína A-I/sangue , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Insulina/sangue , Masculino , Obesidade/genética , Triglicerídeos/sangue , Triglicerídeos/genética
11.
Hand Clin ; 35(1): 7-12, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30470334

RESUMO

This article summarizes the application of local anesthesia no tourniquet in 2 hand surgery centers in China, Nantong and Tianjin, where more than 12,000 patients were operated on with the new approach. This approach achieves excellent anesthetic and vasoconstrictive effects. In Nantong, surgeons performed fracture fixation, soft tissue tumor excision, and flap transfer in the hand with this approach. In Tianjin, surgeons applied it to cases of hand trauma emergency surgery. The authors' experience shows that this approach to hand surgery is safe, economical, and patient friendly, with no increase in infection rate.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/estatística & dados numéricos , Anestesia Local , Mãos/cirurgia , Procedimentos Ortopédicos/estatística & dados numéricos , Anestésicos Locais/administração & dosagem , Atitude do Pessoal de Saúde , China , Difusão de Inovações , Epinefrina/administração & dosagem , Humanos , Lidocaína/administração & dosagem , Vasoconstritores/administração & dosagem
12.
Nat Prod Res ; 33(5): 732-735, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29130339

RESUMO

Multidrug resistance is a major unresolved obstacle to successful cancer chemotherapy. It is often associated with an elevated efflux of a variety of anticancer drugs by ATP-binding cassette transporters including P-glycoprotein, BCRP and MRP1. In this study, the reversal effect of Ethyl lucidenates A on K562/A02 cells was investigated. At concentrations of 10 µM, Ethyl lucidenates A could reverse the resistance of K562/A02 to vincristine up to 7.59 folds. Mechanistically, Ethyl lucidenates A could increase the intracellular accumulation of vincristine in K562/A02 cells through inhibiting the P-glycoprotein mediated drug-transport activity by rhodamine accumulation assay and cell cycle analysis. Further mechanistic investigation found that Ethyl lucidenates A did not alter P-glycoprotein expression. In conclusion, Ethyl lucidenates A could reverse the multidrug resistance of K562/A02 cells via its influence on P-glycoprotein drug-transport activity and thus, be a potential multidrug resistance reversal agent.


Assuntos
Antineoplásicos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Lanosterol/análogos & derivados , Vincristina/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Doxorrubicina/farmacologia , Humanos , Células K562 , Lanosterol/farmacologia , Reishi/química
13.
J Clin Densitom ; 22(3): 321-328, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30205984

RESUMO

Osteoporosis Self-Assessment Tool for Asians (OSTA) is an indicator for assessing osteoporosis in postmenopausal women. The aim of this study was to investigate the value of OSTA index on predicting osteoporosis in elderly Chinese patients with established rheumatoid arthritis (RA). A total of 320 patients with RA and 158 normal individuals were recruited from January 2015 to October 2017. Bone mineral density (BMD) at the femur and lumbar spine was measured by dual-energy X-ray absorptiometry. RA group and control group were divided into low risk (values≥-1), medium risk (values between -4 and -1), and high risk (values ≤-4) group according to the value of OSTA index. One-way analysis of variance showed that BMD at all detected regions among the 3 groups were obviously different (p < 0.0001). Incidences of osteoporosis among different OSTA groups were 21.76% (47/216), 56.41% (44/78), and 80.77% (21/26), separately (x2 = 67.389, p < 0.0001). In RA group including premenspausal or postmenspausal female subgroup, prevalences of osteoporosis among different OSTA groups were different (p < 0.05-0.0001). We also found a positive linear correlation between OSTA index and BMD (p < 0.0001) both in RA and in control groups. Logistic regression revealed OSTA index (odds ratio = 0.734, p < 0.0001, 95% confidence interval: 0.657-0.819) was a protective factor for occurrence of RA-induced osteoporosis. OSTA had the highest discriminatory power, with an estimated Area Under Curve (AUC) of 0.750 (95% confidence interval 0.694-0.807, p < 0.0001), sensitivity of 76.9% and specificity of 66.5%. Our findings indicated that OSTA index was closely associated with BMD in RA patients, the degree of correlation was much stronger than age or BMI. OSTA index was a predictor for osteoporosis in RA, but it might have little relationship with disease status in RA.

14.
Ying Yong Sheng Tai Xue Bao ; 29(12): 4128-4134, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30584741

RESUMO

The construction of highway ecological landscape is an important part of highway entity and an iconic feature of scenic countryside and ecological garden city, which plays an important role in the process of achieving social and economic sustainable development. The efficient index system and method is a basic measurement for the assessment of the interior quality and its associated outer environment. By taking five arterial highways (G15, G228, G204, S334 and S335) in the territory of Nantong City, Jiangsu Province as the case, an evaluation system containing quantitative and qualitative indices was developed to deal with the ecological landscape quality. The system composed of 12 evaluation indices which were divided into three categories including ornamental value, ecological efficiency, and safety design. Based on the survey and calculation of the raw data, the variable matrix was established and analyzed with principal component (PC) analysis. The results showed that the equation of highway greening ecological evaluation score was H=0.694×PC1+0.191×PC2+0.115×PC3, and scores of 5 highways ranked in the ordination of G204 > G15 > S334 > G228 > S335. The results would provide methods and references for efficient evaluation of highway landscape.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , China , Cidades , Ecologia
15.
Radiat Oncol ; 13(1): 194, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30285884

RESUMO

BACKGROUND: Radiation therapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) but also causes transient as well as long-term complications. Patients who develop severe radiation-induced brainstem injuries have a poor prognosis due to the lack of effective medical therapies. However, the relationship between brainstem injury and radiation volume dose is unknown. In this study, we found that radiation-induced brainstem injury was significantly associated with brainstem dose per unit volume. METHODS: A retrospective analysis was performed on a consecutive cohort of 327 patients with NPC receiving IMRT from May 2005 to December 2014. Dose-volume data and long-term outcome were analyzed. RESULTS: The median follow-up duration was 56 months (range, 3-141 months), and six with T4 and two with T3 patients had radiation-induced brainstem injuries. The 3-year and 5-year incidences were 2.2% and 2.8%, respectively. The latency period of brainstem injury ranged from 9 to 58 months, with a median period of 21 months. The Cox regression analysis showed that brainstem radiation toxicity was associated with the T4 stage, D2% of gross tumor volume of nasopharyngeal primary lesions and their direct extensions (GTVnx), Dmax (the maximum point dose), D1%, D0.1cc (the top dose delivered to a 0.1-ml volume), and D1cc (the top dose delivered to a 1-ml volume) of the brainstem (p < 0.05). Receiver operating characteristic (ROC) curves showed that GTVnx D2% and the Dmax, D1%, D0.1cc, and D1cc of the brainstem were significant predictors of brainstem injury. The area under the ROC curve for these five parameters was 0.724, 0.813, 0.818, 0.818, and 0.798, respectively (p < 0.001), and the cutoff points 77.26 Gy, 67.85 Gy, 60.13 Gy, 60.75 Gy, and 54.58 Gy, respectively, were deemed as the radiation dose limit. CONCLUSIONS: Radiotherapy-induced brainstem injury was uncommon in patients with NPC who received definitive IMRT. Multiple dose-volume data may be the dose tolerance of radiation-induced brainstem injury.


Assuntos
Tronco Encefálico/patologia , Carcinoma/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Tronco Encefálico/efeitos da radiação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Prognóstico , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos
16.
Genes Genomics ; 40(10): 1069-1079, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29907909

RESUMO

Although the current glucocorticoids (GCs) treatment for systemic lupus erythematosus (SLE) is effective to a certain extent, the difference in therapeutic effect between patients is still a widespread problem. Some patients can have repeated attacks that greatly diminish their quality of life. This study was conducted to investigate the relationship between HSP90AA2 polymorphisms and disease susceptibility, GCs efficacy and health-related quality of life (HRQoL) in Chinese SLE patients. A case-control study was performed in 470 SLE patients and 470 normal controls. Then, 444 patients in the case group were followed up for 12 weeks to observe efficacy of GCs and improvement of HRQoL. Two single nucleotide polymorphisms (SNPs) of HSP90AA2 were selected for genotyping: rs1826330 and rs6484340. HRQoL was assessed using the SF-36 questionnaire. The minor T allele of rs1826330 and the TT haplotype formed by rs1826330 and rs6484340 showed associations with decreased SLE risk (T allele: PBH = 0.022; TT haplotype: PBH = 0.033). A significant association between rs6484340 and improvement of HRQoL was revealed in the follow-up study. Five subscales of SF-36 were appeared to be influenced by rs6484340: total score of SF-36 (additive model: PBH = 0.026), physical function (additive model: PBH = 0.026), role-physical (recessive model: PBH = 0.041), mental health (dominant model: PBH = 0.047), and physical component summary (additive model: PBH = 0.026). No statistical significance was found between HSP90AA2 gene polymorphisms and GCs efficacy. These results revealed a genetic association between HSP90AA2 and SLE. Remarkably, HSP90AA2 has an impact on the improvement of HRQoL in Chinese population with SLE.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Glucocorticoides/uso terapêutico , Proteínas de Choque Térmico HSP90/genética , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Qualidade de Vida/psicologia , Adulto , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/psicologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
17.
Am J Clin Exp Immunol ; 7(2): 27-39, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755855

RESUMO

Objective: The aim of this study was to investigate the associations between HSP90B1 gene polymorphisms and the efficacy of glucocorticoids (GCs) and the improvement of health-related quality of life (HRQoL) in Anhui patients with systemic lupus erythematosus (SLE). Method: A total of 305 patients with SLE were recruited to the study. These patients were treated with GCs for 12 weeks and classified into two groups (sensitivity and insensitivity) according to the response to GCs measured by the scores on SLE disease activity index (SLEDAI). The HRQoL of SLE patients were evaluated by 36-item Short Form Health Survey (SF-36) at baseline and 12 weeks respectively. HapMap database and Haploview software were used to select HSP90B1 gene tag single nucleotide polymorphisms (SNPs). Benjamini & Hochberg (BH) method based on false discovery rate (FDR) was used for multiple testing correction. Results: A total of 291 patients were included in final data analysis with 14 patients excluded due to loss to follow-up. Among these patients, 160 patients were sensitive to GCs and 131 patients were insensitive to GCs. Twelve tag SNPs of HSP90B1 gene were selected. The rs12426382 polymorphism was associated with the efficacy of GCs (dominant model: crude OR=0.514, 95% CI=0.321-0.824, P=0.006; adjusted OR=0.513, 95% CI=0.317-0.831, P=0.007). After BH correction, there was no association between rs12426382 polymorphism and efficacy of GCs (PBH =0.084). In haplotype analysis, the haplotype CCCGAACATCCC (OR=2.273, 95% CI=1.248-4.139, P=0.006) and CTGGGACGTTC (OR=0.436, 95% CI=0.208-0.916, P=0.025) showed significant associations with the efficacy of GCs. After corrected by BH method, CCCGAACATCCC was still associated with the efficacy of GCs (PBH =0.048). The rs3794241, rs1165681, rs2722188, rs3794240 and rs10861147 polymorphisms were associated with the improvement of HRQoL among SLE patients (P < 0.05). But no association existed after the correction of BH method (P > 0.05). Conclusions: The results of this study demonstrated that HSP90B1 genetic polymorphisms might be associated with the efficacy of GCs, but not associated with the improvement of HRQoL in Anhui population with SLE.

19.
Mol Med Rep ; 17(5): 6472-6482, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29512731

RESUMO

Research advances and analysis in the non­protein coding part of the human genome have suggested that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are associated with tumor initiation, growth and metastasis. Accumulating studies have demonstrated that a class of miRNAs and lncRNAs are dysregulated in hepatocellular carcinoma (HCC) and closely associated with tumorigenesis, diagnosis and prognosis. In the present study, integrative analysis of published data on multi­level Gene Expression Omnibus (GEO) and a bioinformatics computational approach were used to predict regulatory mechanism networks among differentially expressed mRNAs, miRNAs, and lncRNAs. Firstly, nine microarray expression data sets of mRNAs, miRNAs, and lncRNAs associated with HCC were collected from GEO datasets. Secondly, a total of 628 mRNAs, 15 miRNAs, and 49 lncRNAs were differentially expressed in this integrative analysis. Following this, mRNA, miRNA and lncRNA regulatory or co­expression networks were constructed. From the construction of the regulatory networks, five miRNAs and ten lncRNAs were identified as key differentially expressed noncoding RNAs associated with HCC progression. Finally, the regulatory effects of ten lncRNAs and miRNAs were validated. The study provides a novel insight into the understanding of the transcriptional regulation of HCC, and differentially expressed lncRNAs targeted and regulated by miRNAs were identified and validated in HCC specimens and cell lines.


Assuntos
Carcinoma Hepatocelular/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , MicroRNAs/biossíntese , RNA Longo não Codificante/biossíntese , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Neoplásico/genética
20.
J Exp Clin Cancer Res ; 37(1): 53, 2018 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-29530056

RESUMO

BACKGROUND: Ovarian cancer is a deadly disease. Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are frequently dysregulated in ovarian cancer. Overexpression of IAPs proteins has been correlated with tumorigenesis, treatment resistance and poor prognosis. Reinstalling functional cell death machinery by pharmacological inhibition of IAPs proteins may represent an attractive therapeutic strategy for treatment of ovarian cancer. METHODS: CCK-8 and colony formation assay was performed to examine cytotoxic activity. Apoptosis was analyzed by fluorescence microscopy, flow cytometry and TUNEL assay. Elisa assay was used to determine TNFα protein. Caspase activity assay was used for caspase activation evaluation. Immunoprecipitation and siRNA interference were carried out for functional analysis. Western blotting analysis were carried out to test protein expression. Ovarian cancer cell xenograft nude mice model was used for in vivo efficacy evaluation. RESULTS: APG-1387 demonstrated potent inhibitory effect on ovarian cancer cell growth and clonogenic cell survival. APG-1387 induced RIP1- and TNFα-dependent apoptotic cell death in ovarian cancer through downregulation of IAPs proteins and induction of caspase-8/FADD/RIP1 complex, which drives caspase-8 activation. NF-κB signaling pathway was activated upon APG-1387 treatment and RIP1 contributed to NF-κB activation. APG-1387 induced cytoprotective autophagy while triggering apoptosis in ovarian cancer cells and inhibition of autophagy enhanced APG-1387-induced apoptotic cell death. APG-1387 exhibited potent antitumor activity against established human ovarian cancer xenografts. CONCLUSIONS: Our results demonstrate that APG-1387 targets IAPs proteins to potently elicit apoptotic cell death in vitro and in vivo, and provide mechanistic and applicable rationale for future clinical evaluation of APG-1387 in ovarian cancer.

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